International journal of molecular sciences
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Treatment of relapsed and refractory (R/R) B acute lymphoblastic leukemia (B-ALL) represents an unmet medical need in children and adults. Adoptive T cells engineered to express a chimeric antigen receptor (CAR-T) is emerging as an effective technique for treating these patients. Areas covered: Efficacy and safety of CAR-T therapy in R/R B-ALL patients. ⋯ Another way to mitigate waiting is the development of allogeneic "off the shelf" therapy. In conclusion, CD19-targeted CAR-modified T-cell therapy has shown unprecedented results in patients without curative options. Future work focusing on target identification, toxicity management and reducing manufacturing time will broaden the clinical applicability and bring this exciting therapy to more patients, with longer-term remissions without additional Allo-SCT.
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The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19), is a worldwide pandemic, as declared by the World Health Organization (WHO). It is a respiratory virus that infects people of all ages. Although it may present with mild to no symptoms in most patients, those who are older, immunocompromised, or with multiple comorbidities may present with severe and life-threatening infections. ⋯ Appropriate use of these adjunct therapies with antiviral proprieties may be beneficial in the treatment and/or prophylaxis of COVID-19. In this review, we provide a comprehensive summary of nutraceuticals, such as vitamins C, D, E, zinc, melatonin, and other phytochemicals and function foods. These nutraceuticals may have potential therapeutic efficacies in fighting the threat of the SARS-CoV-2/COVID-19 pandemic.
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The ABCG2 gene is a well-established hyperuricemia/gout risk locus encoding a urate transporter that plays a crucial role in renal and intestinal urate excretion. Hitherto, p. Q141K-a common variant of ABCG2 exhibiting approximately one half the cellular function compared to the wild-type-has been reportedly associated with early-onset gout in some populations. ⋯ M131I and p. R236X were functionally deficient and null, respectively. Our findings illustrate why genetic factors affecting ABCG2 function should be routinely considered in clinical practice as part of a hyperuricemia/gout diagnosis, especially in pediatric-onset patients with a strong family history.
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Glioblastoma multiforme (GBM) is amongst the deadliest of human cancers, with a median survival rate of just over one year following diagnosis. Characterized by rapid proliferation and diffuse infiltration into the brain, GBM is notoriously difficult to treat, with tumor cells showing limited response to existing therapies and eventually developing resistance to these interventions. As such, there is intense interest in better understanding the molecular alterations in GBM to guide the development of more efficient targeted therapies. ⋯ This review uses The Cancer Genome Atlas (TCGA) GBM dataset in combination with a data-mining approach to summarize disease characteristics, with a focus on select molecular pathways that drive GBM pathogenesis. We also present a unique genomic survey of RTKs that are frequently altered in GBM subtypes, as well as catalog the GBM disease association scores for all RTKs. Lastly, we discuss current RTK targeted therapies and highlight emerging directions in GBM research.
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Preexisting immunity to SARS-CoV-2 could be related to cross-reactive antibodies to common human-coronaviruses (HCoVs). This study aimed to evaluate whether human milk antibodies against to S1 and S2 subunits SARS-CoV-2 are cross-reactive to S1 and S2 subunits HCoV-OC43 and HCoV-229E in mothers with a confirmed COVID-19 PCR test, in mothers with previous viral symptoms during COVID-19 pandemic, and in unexposed mothers; Methods: The levels of secretory IgA (SIgA)/IgA, secretory IgM (SIgM)/IgM, and IgG specific to S1 and S2 SARS-CoV-2, and reactive to S1 + S2 HCoV-OC43, and HCoV-229E were measured in milk from 7 mothers with a confirmed COVID-19 PCR test, 20 mothers with viral symptoms, and unexposed mothers (6 Ctl1-2018 and 16 Ctl2-2018) using ELISA; Results: The S2 SARS-CoV-2 IgG levels were higher in the COVID-19 PCR (p = 0.014) and viral symptom (p = 0.040) groups than in the Ctl1-2018 group. ⋯ S1 + S2 HCoV-OC43-reactive IgG was higher in the COVID-19 group than in the control group (p = 0.002) but did not differ for the other antibodies; Conclusions: Mothers with a confirmed COVID-19 PCR and mothers with previous viral symptoms had preexisting human milk antibodies against S2 subunit SARS-CoV-2. Human milk IgG were more specific to S2 subunit SARS-CoV-2 than other antibodies, whereas SIgA and SIgM were polyreactive and cross-reactive to S1 or S2 subunit SARS-CoV-2.